Growth promotant substances



United States Patent GROWTH PRQMOTANT SUBSTANCES Alan B. Rogers,Evergreen Park, and John F. Roland, In,

Glenview, Ill., assignors to Armour and Company, Chlcago, 111., acorporation of Illinois No Drawing. Application October 2, 1953 SerialNo. 383,918

11 Claims. c1. 99-2) biotics such as aureomycin. In addition, asreported in the literature in this field, there have been experimentalindications that other. non nutritionalsubstanceaiprinci- 1 Pallysurfactants, er q ei enitiqasinaml t late growth,althoughnottotheextent' pf;1or as-rehably as the antibioticsr-However,asthe-ani't'nal art 2,844,466 Patented July 22, 1958 ice - ability forthe purposes of this inveniton of the class of tive primary, secondaryand tertiary amines.

substances defined above. However, certain sub-classes are preferred.For example, it is preferred that the cationic fragment of the reactionproduct be derived from a surface active quaternay ammonium salt such asthe dimethyl dialkyl ammonium halides of the trimethyl alkyl ammoniumhalides where the alkyl group (or groups) can contain from -8 to 22carbon atoms and can be saturated or unsaturated. Instead of an alkylgroup of the character described, the surface active quaternary"ammonium compound can contain an aromatic group such as a benzyl group.By way of specific example, such cationic surfactants may bementionedas: dimethyl didodecyl ammonium chloride, trimethyl dodecylammonium chloride, diemthyl dioctadecyl ammonium chloride, trimethyloctadecyl ammonium chloride, dodecyl dimethyl benzyl ammonium chloride,octadecyl dimethyl benzyl ammonium chloride, etc. Also, mixtures ofdiiferent cationic surfactants can be employed, such as the naturallyoccurring mixtures where the quaternary ammonium compound is preparedfrom a natural fatty acid source. For example, trimethyl coco ammoniumchloride; dimethyl ditallow ammonium chloride, trimethyl soya ammoniumchloride, etc. are suitable sources for the ctaionic fragments. Inaddition, other cationic surfactants can be used to provide the cationicfragments,such as various surface ac- Usually such amines should containat least 1 alkyl chain having stands at present, only certainafitibiotics have been accepted generally as additives to animal feedsvvhile surfactants have not been lfeltdobe fqf. sufli cient yalue tojustify their use in commercial feedingioperafions; Therefore, there isstill a considerable need for moregeffective and less expensive animalgrowth promotants.

It is therefore a general object of this invention-to provide animalfeeds containing novel growth-promotant substances which comparefavorably with the antibiotics both as to cost and results obtained.Further'o'bjects and advantages will appear as thespecificationproceedag Heretofore it has been postulated that thegrowth-promoting properties of antibiotics and surfactants may berelated to their bactericidal and bacteriostan'c properties. It has alsobeen suggested, particularly in the case of surfactants, that growthstimulation may correlate in some way with surface activity. Therefore,the present invention to a considerable extent goes against priorthinking in the field and, in fact, probably'requires the explanationspreviously advanced for the growth-stimulating effect of surfactants tobe either modified or' abandoned. This is true because the presentinvention is-ba sed' on the discovery that certain classes ofsurfactants 'which' have X been chemically modified so as to displayvirtually no'surface activtiy in water and also so as to possess littleor no bactericidal 'and bacteriostatic properties not only continue toact as growth-stimulants for but-even more surprisingly have proven to-be"greatly superior growth promotants over the unmodified surfactantsfrom which they are formed, and to compare withthe growthgpromotingantibiotics.

The general class offcompounds jwhiclihav'e utility for the purpose ofthis invention can'bedesig'nated as 'the reaction product of --thecationic fragment'of a cationic surfactant with the anionic fragment ofan anionic surfactant. For example, the cationic fragment of itrimethyloctadecyl ammonium chloride can be chemically combined with theanionicfragment of sodium stearate to 'produce trimethyl octadecyl ammoniumstearate, which new compound is then employedforthe-purpose o'f'this Hinvention.

from 8 to 22 carbon atoms. Byway of specific example may be mentioned:octadecyl amine, dimethyl octadecyl amine, bis-hydroxyethyl' octadecylamine, metehyl dioctadecyl amine, dioctadecyl amine, etc. If desired,polyamines like dodecyl trimethylene 'diamine or cyclic nitrogencompounds like octadecyl pyridinium chloride can also be used.

Various anionic surfactants can be used as the source of the anionicfragment in the compounds of this invention. Common soaps, that is,sodium or potassium salts of the higher fatty acids, have provensatisfactory, as for example, sodium stearate or sodium laurate or othersalts of fatty acids containing from 8 to 22 carbon atoms in which thehydrocarbon chains are either saturated or unsaturated. Anionicdetergents are also quite satisfactory, like the alkyl sulphates orsulphonates, as well as the alkyl aryl sulphonates. Also, the alkylmethyl taurides may be mentioned. By way of specific example of the typeof anionic detergents useful in forming the compounds of this inventionmay be mentioned: dodecyl sulphate, octadecyl benzene sodium sulphonate,the ester of oleic acid and hydroxy ethane sodium sulphonate, etc. Thequaternary ammonium soaps can be considered as typical of the compoundsof this invention, that is, as the reaction product of a surface activequaternary ammonium compound and a soap. Such reaction products arequite insoluble in water and display substantially no surface activityin water as distinguished from both the anionic and cationic surfactantsfrom which they are formed. Further, these reaction products have littlegermicidal activity as compared with the compounds from which they areformed. In spite of these modified properties, however, it has beenfound that these reaction products are surprisingly effective inpromotingthe growth of various animals and, in particular, inpromoting'the growth of hogs and chickens.

In practicingthis invention, the reaction products deof the animalswithout having any undesirable toxic effect on the animal. Therefore, itis relatively easy to practice the invention by incorporating thecompounds in animal feeds or other nutrient materials which will beconsumed by the animals. In this way it has been found possible toincrease the rate of weight gain as much as 8 to 15% on the average inchickens, and a comparable although somewhat lesser amount in hogs. Thefeed eficiency is also significantly improved, i. e., the pounds of feedrequired to produce one pound of weight gain are decreased.

The following examples more fully illustrate this invention bydescribing tests with animal feed materials characterized by containingas an essential ingredient therein at least one compound composed of thecationic fragment of a cationic surfactant and an anionic fragment of ananionic surfactant.

EXAMPLE I Trimethyl octadecyl ammonium stearate was tested as a growthpromotion for baby pigs fed on synthetic milk. The results of thesetests are summarized below:

Average weekiz Over Preceding No. oi P ll 8 4 Weeks Weeks 1 Week Foodmaeu gge matter ted/lb. Lot

1 8 4 Week W Weeks Weeks Weeks Lot 1-Fed synthetic milk plus trimethylostsdeeyl ammonium atearate Lot a-Fad synthetic milk plus aureomyein Lot3-Fed synthetic milk Levels oi promotant ted milk dry matter):

Trimethyl ostedeeyl ammonium steante so mgJkg. ior first three weeks, 6500 mgJkg. aiter three wee Anreomyoin 0 60 mgJkg. throughout thefive-week period Average gain and feed efiiciency for 3-week period(weeks I, 2 and 3) Gain, lbs. Emoienoy Lot Lot Lot Average gains andfeed efliciency for 4th and 5!]: weeks of test Gain lbs. Emeiency is 19as r-rr The above data indicate that for the baby pig on a milk diettn'methyl octadecyl ammonium stearate is preferably used atconcentrations above 50 mg. per kilogram of dry matter and is eiiectiveat concentrations up to at least 500 mg. per kg.

' EXAMPLE lI Fnrthetteatsweremadewithtrimethyloctadecylam moniumstearate on weanling pigs with the following results:

Ave. Average Daily Gains Over Initial Wt., Lbs. Initial Lot WL,

Lbs. 2 4 6 8 10 Weeks Weeks Weeks Weeks Weeks Feed Efllclency (lbs.feed/lbs. gain) Lot 2 Weeks 4 Weeks 6 Weeks 8 Weeks 10 Weeks 2. 37 2. 662. 6i 2. 76 2 94 2. 26 1 4e 2. 63 2. 84 3. 03 6.-- 2. 18 2. 44 2. so 2.72 7. 90 8.-. 2. 28 2. 62 2. 01 2. 81 8. 02

Lot 1--Fed basal ration Lot 2-Fed basal ration plus Auroisc 5 lbsJtonLot 0-.Fed besairation plus trimethyl ostedecyl ammonium stearate Q 60[ton Lot 6- ed basal ration plus trimethyl octadecyl ammonium stearate 625 gun/ton Basel ration: Cor 807 bean oil meal Meat and bone mp Fishmlnhlm 15 1 50101 h 1min um Iodised ml? up Trace minerals- Vitamins Aand D 0. Fortaieed 2-0-0 EXAMPLE [[1 The efiect of trimethyl octadecylammonium stearate on the growth of chicks was shown in the followingtest:

1 Trlmethyl ostadeeyl ammonium stearate added to ration 12% mg./

Gm u o/bcsoi ration: M o m 0 corn....

ed sk. milk... a 0

Meet straps... 4.0

mm! a 5 8t. bone meal 1. ll

am uni- Vitamin pie-mix Provides per pound oi diet: Riboflavin 1 mNiacin 17 mg., Cs pantothenate 2.5 mf. vitaminBu 1.5 mcg.,oho e chloride22'! mg., a two units, 1) soc do.

EXAMPLE 1V Further tests were made as described in Example 111, exceptthat the basal ration contained 62.0% yellow corn and 2.0% animal fat.The results were as follows:

Average gains in weight 'l est No. Int

(weeks, Bweeks,

.gm. gm.

Feed efiiciency l firgimethyl octadecyl ammonium stearate added toration 12% mg.

EXAMPLE V The following compounds were incorporated in the basal diet ofweanling rats to determine their effect as growth stimultants:

(a) Trimethyl octadecyl ammonium stearate;

(b) Trimethyl octadecyl ammonium dodecyl sulphate;

(c) Trimethyl octadecyl ammonium alkyl benzene sulphonate', and

(d) Trimethyl octadecyl ammonium oleylmethyl tauride.

Eight rats per lot were tested, and the data given below reports theresults on the second week of the tests. There is always a readjustmentperiod when placing weanhng rats on a diet and it is thus consideredthat the data on the first week may not be significant. The rats weretaken off test after the 2-week period:

Level mg./ Gain in Wt. Promotant kilo of feed (7 to 14th day), GramsBasal diet: Casein to rovide 97 protein Cerelose 587 lard 28.07 salt mixU. S. P. N o. 2, 4 and adquate aniounts oi esseniial-vitamins,

EXAMPLE VI A number of additional tests were run employing compoundsfalling within the scope of this invention as additives to chicken feedcomposed of a basal ration similar to that described in Example IH. Asummary of these tests is set out below, the weights at 4, 6, and 8weeks being given in grams.

Summary of feed efiiciency in above experiment:

Feed/pound gain to 8 weeks Basal 2.86 Basal-l-A-l 2.71 Basal +A-2 2.72Basal-i-A-3 2.79 Basal-l-A-4 2 64 Summary of growth response in grams ofchicks to additions of A-2 to the diet:

'Age (Weeks) 4 6 8 Basal 377 666 1, 115 396 688 1, 134 4% 740 1, 222 408715 1, 138

The compound identification symbols used in this example have thefollowing meaning:

A1-trimethyl octadecyl ammonium stearate A2-trimethyl octadecyl ammoniumdodecyl sulphate A-3--trimethyl octadecyl ammonium dodecyl benzenesulphonate A4tn'methyl octadecyl ammonium oleylmethyl tauride Inpreparing the hog and chicken feed materials described in the aboveexamples, the growth-promotant substance, such as trimethyl octadecylammonium stearate, were intimately mixed with another feed ingredient,such as one of the commonly used feed ingredients like bone meal orlimestone, to produce 5% to 10% premix. An appropriate amount of thispremixjwas then distributed throughout the entire feed in a feed mixer.The premix can be made conveniently in'any mixer which provides agrinding action in addition to stirring. 'Alternatively thegrowth-promotant substance can be dissolved in a solvent, such asethanol, propanol-Z, etc., and the solubilized material mixed with thebone meal or other commonly used feed ingredient as described above.

The range of effectiveness of the growth-promotant substances of thisinvention depends on the age and species of the animal being fed.Experiments have shown response from 12 grams up to 500 grams per ton offeed. A favorable range for growing poultry and swine appears to beabout 25 to 200 grams per ton of feed. However, greater or lesseramounts can be employed with considerable success.

The growth-promotant substances described herein not only speed upgrowth. of the animal, but also improve the efficiency of feedconversion. This is an important advantage, since it makes the growingprocess more economical for animal raisers by requiring less feed perpound of weight gain.

While in the foregoing specification this invention has been describedin relation to certain specific embodiments thereof and many detailshave been set forth for purpose of illustration, it will be apparent tothose skilled in the art that the invention is susceptible to otherembodiments than those set forth and that many of the specific detailscan be varied widely without departing from the basic concepts of theinvention.

We claim:

1. An animal nutrient material characterized by containing as anessential ingredient therein at least one compound composed of thecationic fragment of a quaternary ammonium surfactant and the anionicfragment of an anionic surfactant, said compound being substantiallyinsoluble and non-surface active in water.

2. The animal nutrient material of claim 1, in which said quaternaryammonium surfactant is a trimethyl octadecyl ammonium surfactant.

3. The animal nutrient material of claim 1, in which said compound istrimethyl octadecyl ammonium stearate.

4. A hog feed material characterized by containing as an essentialingredient therein at least one compound composed of the cationicfragment of a quaternary ammonium surfactant and the anionic fragment ofan anionic surfactant, said compound having the function of a growthpromotant in said feed material while being substantially insoluble andnon-surface active in water.

5. A chicken feed material characterized by containing as an essentialingredient therein at least one compound composed of the cationicfragment of a quaternary ammonium surfactant and the anionic fragment ofan anionic surfactant, said compound having the function of a growthpromotant in said feed material while being substantially insoluble andnon-surface active in water.

6. The animal nutrient material of claim 1, in which said quaternaryammonium surfactant is trimethyl alkyl ammonium salt inn which the alkylgroup contains from 8 to 22 carbon atoms.

7. An animal feed material characterized by contaiw ing as anessentialingredient therein at least one compound composed of thecationic-fragment of a cationic surfactant and the anionic fragment ofan anionic surfactant, said cationic surfactant being selected from thegroup consisting of quaternary ammonium surfactants and cyclic nitrogensurfactants, said anionic surfactant being selected from the groupconsisting of fatty acid salt surfactants, alkyl sulphate surfactants,alkyl aryl surfactants, and alkyl methyl tauride surfactants.

8. The animal feed material of claim 7 in which the ingredient is aquaternary ammonium soap, said ingredient being substantially insolubleand non-surface active in water.

9. The animal feed material .of claim 7 in which the ingredient istrimethyl ammonium dodecyl sulphate.

10. The animal feed material of claim 7 in which the ingredient istrimethyl octadecyl ammonium dodecyl benzene sulfonate.

11. The animal feed material of claim 7 in which the ingredient istrirnethyl octadecyl ammonium oleylmethyl tauride.

References Cited in the file of this patent UNITED STATES PATENTS OTHERREFERENCES Ely et al.: Proc. Distillers Feed Conference, March

1. AN ANIMAL NUTRIENT MATERIAL CHARACTERIZED BY CONTAINING AS ANESSENTIAL INGREDIENT THEREIN AT LEAST ONE COMPOUND COMPOSED OF THECATIONIC GRAGMENT OF A QUATERNARY AMMONIUM SURFACTANT AND THE ANIONICFRAGMENT OF AN ANIONIC SURFACTANT, SAID COMPOUND BEING SUBSTANTIALLYINSOLUBLE AND NON-SRUFACE ACTIVE IN WATER.